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2. Pregabalin and Gabapentin for GAD (Node 3A)
David N. Osser, MD
Associate Professor of Psychiatry
Harvard Medical School
Brockton Division of the VA Boston Healthcare System
General Editor - Psychopharmacology Algorithm Project
Harvard South Shore Residency Training Program

3. Pregabalin Not approved in U.S. for GAD Rejected twice
Why?
Not superior to placebo?
Safety?
Approved in Europe and South America for GAD
7 positive RCTs
Bech, P. (2007). Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials. Pharmacopsychiatry, 40(04),
Wensel, T. M., Powe, K. W., & Cates, M. E. (2012). Pregabalin for the treatment of generalized anxiety disorder. Annals of Pharmacotherapy, 46(3),

4. Pregabalin Compared to SSRIs: rapid onset, helps with insomnia
Dose-dependent effect: > 300 mg/day more effective
Caution in elderly: falls and somnolence
Bech, P. (2007). Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials. Pharmacopsychiatry, 40(04),
Wensel, T. M., Powe, K. W., & Cates, M. E. (2012). Pregabalin for the treatment of generalized anxiety disorder. Annals of Pharmacotherapy, 46(3),

5. Pregabalin vs. Gabapentin
Gabapentin: lower cost
Very similar compound & chemical structure
Frequently used off-label use as anxiolytic
Clarke, H., Kirkham, K. R., Orser, B. A., Katznelson, R., Mitsakakis, N., Ko, R., ... & Katz, J. (2013). Gabapentin reduces preoperative anxiety and pain catastrophizing in highly anxious patients prior to major surgery: a blinded randomized placebo-controlled trial. Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 60(5),

6. Pregabalin vs. Gabapentin
Trial in 420 women with breast cancer
Dose: 300mg and 900mg
Superior to placebo for anxiety
No studies in GAD
Concerns for misuse
Lavigne, J. E., Heckler, C., Mathews, J. L., Palesh, O., Kirshner, J. J., Lord, R., ... & Mustian, K. (2012). A randomized, controlled, double-blinded clinical trial of gabapentin 300 versus 900 mg versus placebo for anxiety symptoms in breast cancer survivors. Breast cancer research and treatment, 136(2),
Schifano, F., D’Offizi, S., Piccione, M., Corazza, O., Deluca, P., Davey, Z., ... & Mannonen, M. (2011). Is there a recreational misuse potential for pregabalin? Analysis of anecdotal online reports in comparison with related gabapentin and clonazepam data. Psychotherapy and psychosomatics, 80(2),
Smith, R. V., Lofwall, M. R., & Havens, J. R. (2015). Abuse and diversion of gabapentin among nonmedical prescription opioid users in Appalachian Kentucky. American Journal of Psychiatry, 172(5),

7. Next Presentation - Bupropion for GAD